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N Rizzuto

Publications and source records attributed to N Rizzuto.

At least 91 records · Page 5Linked to original sources
PubMed1996

Sensory involvement in X-linked spino-bulbar muscular atrophy (Kennedy's syndrome): an electrophysiological study.

Electrophysiological findings were studied in a family with spino-bulbar muscular atrophy (SBMA): the subjects were three male patients aged 58, 38 and 34 years and two female carriers aged 63 and 28 years. Diagnosis was proven at the molecular genetic level. Electromyography in the males showed spontaneous activity and neurogenic reorganization of the motor unit; motor nerve conduction was normal. Sensory action potentials were variably reduced in amplitude, but some were completely normal. Somatosensory evoked potentials, from both the upper and lower limbs, were invariably abnormal because involvement of the central pathways was observed. These findings are in agreement with histological investigations documenting lesions in the posterior columns. Brain-stem acoustic evoked potentials showed an increase in wave I latency. The electrophysiological data provide further evidence of the extent of sensory damage either in the central or the peripheral nervous system in SBMA patients, who otherwise have a constant clinical presentation of progressive motor neuron disease.

Adult↗
PubMed1996

Expression and regulation of glial-cell-line-derived neurotrophic factor (GDNF) mRNA in human astrocytes in vitro.

The expression and modulation of mRNA for glial-cell-line-derived neurotrophic factor (GDNF) in human glial cells was investigated. Astrocyte cell cultures were isolated from human fetal brains, characterized by immunocytochemistry and maintained in vitro in conditions of high purity; sister cultures were exposed to protein kinase C (PKC) inhibitors for 20 min. Total RNA was extracted from the cell pellets, reverse-transcribed into cDNA and amplified by the polymerase chain reaction (PCR) with primers specific for GDNF. A reverse-transcription/PCR procedure was also performed on mRNA extracted from human fibroblast and lymphocyte cell lines. Human astrocytes grown in the absence of neurons expressed detectable amounts of mRNA for GDNF but no amplification products were observed in fibroblasts and lymphocytes, thus confirming that GDNF production was cell-type specific. After exposure to PKC inhibitors, a dramatic down-regulation of GDNF mRNA was observed in astrocyte cell cultures. Thus, human astrocytes are constitutively capable of producing GDNF, such trophic activity is restricted to neural cells, and PKC plays key roles in signal pathways that regulate the gene activation and production of GDNF.

Astrocytes↗
PubMed1996

Motor neuron disease with pyramidal tract dysfunction involves the cortical generators of the early somatosensory evoked potential to tibial nerve stimulation.

We evaluated somatosensory evoked potentials (SEPs) to tibial nerve stimulation in 39 patients with sporadic motor neuron disease using multiple scalp derivations (earlobe reference). SEPs were altered in 22 of 29 amyotrophic lateral sclerosis (ALS) patients, whereas they were unaffected in 10 progressive muscular atrophy (PMA) patients. The main changes involved the amplitude and the field distribution of the early P40 and N37 cortical potentials with different modalities varying from a selective loss of the P40 potential (33% of tested sides) to absence of all early cortical SEPs (22% of tested sides). The later components following N50 were generally spared. The commonly used Cz-Fz montage was inadequate for detecting these alterations. Central afferent conduction was slightly affected. The selective loss of cortical SEPs and their close correlation with clinicoelectrophysiologic evidence of central motor system involvement strongly support a cortical origin of the SEP alterations in ALS. We suggest that neuronal loss in the somatosensory cortex may selectively affect the generator sites of the cortical SEPs to lower limb stimulation.

Adult↗
PubMed1996

Cytoskeletal changes in cultured human fibroblasts following exposure to 2,5-hexanedione.

In the present study, the effects of the 2,5-hexanedione (HD) on the various cytoskeletal components of human eukaryotic cells were investigated. Primary cultures of human fibroblasts from three healthy donors were exposed to 2.8 mM HD for 14 days; unexposed cultures were used as controls. At different time intervals, cells were counted and the growth curves compared. After 14 days of treatment, the cultures were processed for immunoblotting, immunocytochemistry and ultrastructural studies. As compared to controls, morphological abnormalities induced by HD consisted of modification of the cell shape, formation of tangles composed by 10 nm filaments and cytoplasmic segregation of microtubules and membrane-bound organelles. By immunocytochemistry, the tangles of cytoplasmic filaments were stained by an antibody specific for vimentin. By immunoblotting, the anti-vimentin antibody recognized only bands of 50-60 kDa. Comparison of growth curves between treated and control fibroblasts clearly revealed an interference of HD with the cell cycle. The present results demonstrate that the cytotoxicity of HD is not restricted to intermediate filaments, but affects other cytoskeletal components, such as microtubules, as suggested by the impairment of cell division cycle.

Cell Count↗
PubMed1995

A common beta hexosaminidase gene mutation in adult Sandhoff disease patients.

beta-Hexosaminidase gene mutations were analyzed in two adult-onset Sandhoff disease Italian patients by PCR analysis of a common known mutation (delta 5') and by heteroduplex analysis of genomic and RT-PCR DNA fragments, covering the whole gene. The patients' genotypes were delta 5'/C1214%, and G890A/C1214T, respectively. As mutation C1214T (Pro405Leu) is also present in the other two late-onset cases so far described, we suggest that C1214T is a common mutation in this type of Sandhoff disease. Mutation G890A (Cys297Tyr) is a novel mutation which presumably causes altered processing of the pro beta chain.

Adult↗
PubMed1995

Role of HIV in the pathogenesis of distal symmetrical peripheral neuropathy.

We report the results of a clinical, electrophysiological and pathological study conducted in 18 AIDS patients presenting a distal symmetrical predominantly sensory polyneuropathy (DSPN) characterized by painful dysesthesias as main complaint. Onset of the neuropathy was at CDC (Center for Disease Control) stage II in 2 patients, at CDC stage III in 5 patients and at CDC stage IV in the remainder. Electrophysiological investigation confirmed the presence of an axonal alteration in the sensory nerves, but also revealed motor involvement in all cases. The neuropathological features of sensory nerves were fiber loss and axonal degeneration with macrophagic activation. The expression of monocyte-macrophage markers and of major histocompatibility complex class II antigens appeared up-regulated in endoneurial ramified cells, while expression of CR3, a complement receptor involved in the process of phagocytosis, was down-regulated. In six nerve biopsy samples and in two out of five DSPN dorsal root ganglia we found HIV-related mRNA and protein located in scattered cells of the endoneurium which we presume to be macrophages. These data suggest that: (a) DSPN may occur early in the course of the disease and is not limited to later stages; (b) DSPN is not a ganglionitis but is actually a sensory-motor neuropathy; (c) the virus enters the peripheral nervous system and induces changes in the immunocompetent cell population with activation of macrophages. Storage of the virus inside macrophages may act both as a reservoir for the virus and as a putative cause of nerve damage, probably through release of cytotoxins and/or interaction with trophic factors.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Brain metastases from post-radiation malignant peripheral nerve sheath tumour.

A 45-year-old female patient developed a malignant peripheral nerve sheath tumour (MPNST) arising from the left brachial plexus, ten years after regional radiation treatment for Hodgkin's disease. The clinical course was characterized by local recurrence, pulmonary and cerebral metastases with endocranic hypertension syndrome, and the death of the patient 18 months after the onset of symptoms. The tumour presented a histopathological picture of schwannoma with a high grade of malignancy. A particular feature of this case was the exceptional occurrence of the early and massive invasion of the brain.

Brain Neoplasms↗
PubMed1995

Systemic passive transfer studies using IgM monoclonal antibodies to sulfatide.

We present a patient with benign IgM-gamma anti-Sulfatide (SUL) whose neuropathy was transferred in newborn rabbits. The patient's clinico-pathological picture of anti-SUL-associated demyelinating neuropathy is reported. The monoclonal IgM antibodies prepared by Tatum's method, that retained their biological activity, were passively transferred to newborn rabbits. The passive transfer produced demyelinating nerve lesions very similar to the donor antibody neuropathy. In experimental lesions we observed the human IgM anti-SUL antibodies binding to Schmidt-Lanterman incisures and nodes of Ranvier. We postulate that the myelin-specific and complement-dependent lesions observed in the peripheral nerve support the potential demyelinating role of anti-SUL antibodies. Moreover, the pattern of the antibody binding to the perineuronal sheath of satellite cells in dorsal root ganglia strengthen the hypothesis that anti-SUL antibodies may have a pathogenetic role in this sensorimotor syndrome.

Aged↗
PubMed1995

Tau protein immunolocalization in fetal and adult human spinal cord.

In the present study, the monoclonal antibody Alz-50 has been used to determine and compare the immunohistochemical localization of phosphorylated tau proteins in the developing and normal adult spinal cord. At all stages of fetal life Alz-50 fiber immunoreactivity was observed in the dorsal roots, in the dorsal and dorsolateral funiculi, and in restricted regions of the dorsal horn. Alz-50 immunoreactivity was also demonstrated in the dorsal root ganglion neurons. In the adult spinal cord a consistent pattern of Alz-50 fiber immunoreactivity was localized in the superficial layers of the dorsal horn (lamina I and II) but not in dorsal and dorsolateral funiculi and in the dorsal root ganglion. Comparable results in fetal specimens have been obtained employing PHF-1, a monoclonal antibody generated against paired helical filament proteins from Alzheimer brains, while no significant immunostaining for PHF-1 was observed in the adult spinal cord. In addition, the staining with monoclonal and polyclonal anti-tau antibodies overlapped with that of Alz-50. The transient, selective pattern of Alz-50 and PHF-1 immunoreactivity may disclose some relevant functions of tau proteins during somatosensory pathway development.

Adult↗
PubMed1995

Autoimmune paraneoplastic cerebellar degeneration: immunohistological localization of antibody-binding sites.

Sera from 3 patients with breast or ovarian tumors and paraneoplastic cerebellar degeneration (PCD) contained anti-Purkinje cell antibodies (PCAbs) which also bind to other neurons on frozen sections of adult rodent brain. PCAbs tested on new-born rodent (rabbit, rat, mouse) brain tissue detected only oligodendrocyte-like cells (ODLC) in the white matter and allowed us to speculate on the nature of the antigenic structure in the neuronal cytoplasm. All these PCAbs appear histochemically identical and recognize antigens which belong to so-called "Yo" proteins.

Adenocarcinoma↗
PubMed1995

Experimental induction of myelin changes by anti-MAG antibodies and terminal complement complex.

We investigated the role of anti-myelin-associated glycoprotein (MAG) IgM and complement (C) in the pathogenesis of myelin alterations occurring in patients with anti-MAG-associated polyneuropathy. For this purpose, we separately studied the effects of anti-MAG antibodies and terminal C complex (TCC) after injection into the rabbit sciatic nerve. The two different local treatments produced identical ultrastructural abnormalities such as intramyelinic edema, myelin vesiculation and, in particular, separation of the major dense lines with the formation of widely spaced myelin, a peculiar feature encountered in human peripheral nerve disorders with circulating anti-myelin monoclonal IgM. In nerves treated with anti-MAG IgM ultrastructural myelin alterations were concurrent with activation of the rabbit's own C to the formation of TCC. Contrary to the immunological and ultrastructural findings obtained in C-sufficient animals, in C6-deficient rabbits injected with anti-MAG IgM no myelin alterations nor C completion were observed. This study identifies anti-MAG IgM as the mediator and the C as the effector of myelin changes observed in the present model and, for extension, in human neuropathies associated with anti-MAG IgM.

Animals↗
PubMed1995

Expression and distribution of GAP-43 in human astrocytes in culture.

By combining mRNA analysis and immunocytochemistry, we investigated the expression of the growth associated protein 43 (GAP-43) in enriched populations of astrocytes, obtained from mixed cultures of human fetal brains. Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA; cDNA was subjected to PCR amplification using primers specific for GAP-43 and PCR products were separated through polyacrylamide gels. Double immunofluorescence staining was performed on dissociated cell cultures using antibodies to glial fibrillary acidic protein (GFAP) and to GAP-43. Results showed that both transcription and translation for GAP-43 occur in cultured astrocytes. GAP-43 immunoreacting material was detected in the cell processes and diffusely in the cytoplasm of GFAP-positive astrocytes, during early stages of maintenance in vitro. In older cultures, GAP-43 immunoreactivity persisted in a large percentage of cells, with a tendency to accumulate in perinuclear areas. These observations provide evidence that GAP-43 is not restricted to neuronal cells. The close spatial association with cytoskeletal constituents, as observed in astrocytes, suggests a role for this protein in the control of cell shape, motility and adhesion processes.

Astrocytes↗
PubMed1994

Microgyria associated with Sturge-Weber angiomatosis.

A case is reported of an infant affected with Sturge-Weber disease who underwent left hemispherectomy due to untreatable seizures when 97 days old. Pathological analysis of the surgical specimens revealed the presence of four-layered microgyric cortex below the angiomatosis, intense gliosis, and the presence of calcifications of both the abnormal cortex and the underlying white matter. These findings suggest that the early infantile form of Sturge-Weber disease is associated with a developmental disorder of the cortical organization. Such abnormalities are consistent with the presence of an epileptogenic condition that is unresponsive to pharmacological treatment.

Atrophy↗
PubMed1994

Pattern of nervous tissue immunostaining by human anti-glycolipid antibodies.

Immunostaining of human, bovine and rodent unfixed nervous tissue sections was performed in order to characterize the structures recognized by anti-glycolipid antibodies. Four human sera from patients, two with M-IgM and motor neuron syndrome or motor neuropathy and two with motor neuropathy and polyclonal IgG antibody activity against gangliosides (GL; i.e. GM1, GD1b, GD1a), were utilized. Serum from a patient with sensory neuropathy and M-IgM immunoglobulins with antibody activity against sulfatide (SUL) was included in this series. This study shows that polyclonal and monoclonal anti-glycolipid antibodies give three different patterns of staining. The first is cholera toxin-like showing a more restricted neuronal pattern of staining. The second is peanut agglutinin-like, which includes the carbohydrate epitope shared by a group of glycoproteins in the gray and white matter. The third (anti-SUL) gives a preferential myelin staining. However, sera with anti-GM1 and anti-SUL antibodies recognize a number of closely situated determinants in the gray matter of the spinal cord and in the granule cells, while in peripheral nerves or in neuronal cells in culture their binding produces a different pattern (nodes of Ranvier for anti-GL; myelin for anti-SUL). These findings indicate that immunohistochemistry with anti-GL and anti-SUL antibodies may provide information regarding the glycolipid-bearing anatomical structures as target antigens and further substantiate the role of these molecules in the pathogenesis of autoimmune neurological disorders.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Spinal somatosensory evoked potentials in patients with tethered cord syndrome.

We studied the electrophysiological changes occurring in six patients with tethered cord syndrome. Evidence of spinal malformations was provided by magnetic resonance imaging. The functional assessment of the spinal cord was performed by analysing both spinal and cortical somatosensory evoked potentials. The evoked electrospinogram was recorded from the thoracic and lumbosacral spinous processes. The N22 lumbosacral potential was selectively affected, being rostrocaudally displaced and reduced in amplitude or even absent in patients with neurological signs indicating a segmental lower cord lesion. Inter-peak somatosensory evoked potentials latency was normal in all cases, suggesting that ascending axonal potentials in the dorsal column fibres may be synchronized. Segmental potentials of the lumbosacral response, originating from the post-synaptic activity of dorsal horn interneurons, are selectively affected in this syndrome resulting from the rostrocaudal displacement of the spinal cord due to tethering. Our findings in the clinical field are consistent with previous experimental evidence indicating a different sensitivity of the gray vs. white matter to progressive stretching.

Adult↗